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Mineralocorticoid Receptor May Regulate Glucose Homeostasis through the Induction of Interleukin-6 and Glucagon-Like peptide-1 in Pancreatic Islets

1
Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
2
Food and Health Sciences, Prefectural University of Kumamoto, Kumamoto, 862-8502, Japan
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(5), 674; https://doi.org/10.3390/jcm8050674
Received: 11 April 2019 / Revised: 8 May 2019 / Accepted: 9 May 2019 / Published: 14 May 2019
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
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Abstract

Because the renin-angiotensin-aldosterone system influences glucose homeostasis, the mineralocorticoid receptor (MR) signal in pancreatic islets may regulate insulin response upon glucose load. Glucagon-like peptide-1 (GLP-1) production is stimulated by interleukin-6 (IL-6) in pancreatic α-cells. To determine how glucose homeostasis is regulated by interactions of MR, IL-6 and GLP-1 in islets, we performed glucose tolerance and histological analysis of islets in primary aldosteronism (PA) model rodents and conducted in vitro experiments using α-cell lines. We measured active GLP-1 concentration in primary aldosteronism (PA) patients before and after the administration of MR antagonist eplerenone. In PA model rodents, aldosterone decreased insulin-secretion and the islet/pancreas area ratio and eplerenone added on aldosterone (E+A) restored those with induction of IL-6 in α-cells. In α-cells treated with E+A, IL-6 and GLP-1 concentrations were increased, and anti-apoptotic signals were enhanced. The E+A-treatment also significantly increased MR and IL-6 mRNA and these upregulations were blunted by MR silencing using small interfering RNA (siRNA). Transcriptional activation of the IL-6 gene promoter by E+A-treatment required an intact MR binding element in the promoter. Active GLP-1 concentration was significantly increased in PA patients after eplerenone treatment. MR signal in α-cells may stimulate IL-6 production and increase GLP-1 secretion, thus protecting pancreatic β-cells and improving glucose homeostasis. View Full-Text
Keywords: Mineralocorticoid receptor (MR); Glucagon-like peptide-1 (GLP-1); interleukin-6 (IL-6); α-cells; glucose homeostasis Mineralocorticoid receptor (MR); Glucagon-like peptide-1 (GLP-1); interleukin-6 (IL-6); α-cells; glucose homeostasis
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Goto, R.; Kondo, T.; Ono, K.; Kitano, S.; Miyakawa, N.; Watanabe, T.; Sakaguchi, M.; Sato, M.; Igata, M.; Kawashima, J.; Motoshima, H.; Matsumura, T.; Shimoda, S.; Araki, E. Mineralocorticoid Receptor May Regulate Glucose Homeostasis through the Induction of Interleukin-6 and Glucagon-Like peptide-1 in Pancreatic Islets. J. Clin. Med. 2019, 8, 674.

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